Nerve stimulators commercially available for targeted nerve therapies are exemplified by the NeuroTrace III (HDC Corp., Milpitas, Calif.), the Stimuplex (B. Braun America, Bethlehem, Pa.) and the Digistim III (NeuroTechnologies, Inc, Chennai, India), among others. These devices are constant current, monophasic, pulsed square waveform generators having pulse widths no longer than 200 microseconds in duration. These devices are connected to insulated hypodermic needles which are inserted through the skin and advanced toward the presumed position of a target nerve. Accurate localization of the needle tip is presumed when either a sensory paresthesia or a motor paresthesia is provoked by current outputs less than 0.5 mA. This work is derived from historical strength-duration curves. However, there are several problems with these devices.
The following references will be used to discuss relevant prior art and inadequacies.
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3. Barthram C N. Nerve Stimulators for Nerve Location—Are They All the Same? Anaesthesia 1997; 52:761–4.
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6. Hadzic A; Vloka J, Hadzic N, Thys D M, Santos A C. Nerve stimulators used for peripheral nerve blocks vary in their electrical characteristics. Anesthesiology 2003; 98(4):969–74.
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10. Hille B. Ionic Basis of Resting and Action Potentials. Brookhart, J. M., Mountcastle, V. B., and Kandel, E. R. The Nervous System. Baltimore, Md.: Waverly Press, Inc; 1977. pp. 99–136.
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12. Cole K S, Membranes, ions, and impulses. Berkeley and Los Angeles: University of California Press; 1972. (Biophysics Series; 1).
13. Rall W. Core Conductor Theory and Cable Properties of Neurons. Brookhart, J. M., Mountcastle, V. B., and Kandel, E. R. Handbook of Physiology, section 1, The Nervous System. Baltimore, Md.: Baltimore, Md.; 1977. pp. 39–97.
Cooper (reference 1 above) developed a mathematical description of the necessary parameters of externally applied, pulsed electric fields for effective nerve stimulation. There are two important concepts that derive from his work. First, an adequate voltage gradient must be generated across the neuronal cell membrane for effective depolarization of the nerve cell to occur. Second, an externally applied electric field must have a pulse duration that is at least 0.5 times the neuronal cell membrane time constant to cause reproducible depolarization.
Anesthesia literature is replete with papers concerning nerve stimulation. In all of these works, the applied current is seen as an important parameter (references 2–9). However, examination of the Hodgkin-Huxley equations reveals that current does not play a role in the opening of membrane sodium or potassium channels. Opening of these channels is required for nerve depolarization to occur (see references 10–12). The role that applied current plays in nerve depolarization is related to the associated voltage gradient required to drive the current through the load represented by the tissue impedance. At a first level approximation, the current to voltage relationship follows Ohm's Law, or E=I· R, where E is voltage, I is current, and R is resistance. Clearly, at constant current, the voltage will vary directly with the load. During placement of a needle for nerve stimulation, the load varies with distance from the nerve, as shown by Nervonix experimental data in FIG. 1. Since the impedance decreases as the needle tip approaches the nerve, the applied voltage will also decrease, making the development of an adequate voltage gradient for depolarization unpredictable.
An additional factor in achieving adequate voltage with constant current output is the resistance/capacitance (RC) nature of tissue. Tissue can be represented in equivalent electrical circuits as an RC circuit. When any RC circuit is exposed to a constant current pulse, the associated voltage shows a charging curve as depicted from Nervonix experimental data in FIG. 2. A constant current pulse was directed across tissue via a 22 G insulated needle or a 24 G insulated needle. These data demonstrate that the applied voltage only reaches its maximum toward the end of the 2.5 ms pulse. If the pulse had ended at 0.2 ms, as the commercially available nerve stimulators provide, the voltage would be well short of its maximum value.
Finally, there are a many references regarding the time constant of motoneurons. Rall (reference 13) summarizes these studies, which show that motoneuron membrane time constants range from 3 ms to 7 ms. Based on Cooper's work, if a pulse is to be of adequate duration to reproducibly cause neuronal cell depolarization, it must be greater than 1.5 ms. The commercially available nerve stimulators operate well below this level.